Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the world, causing serious adverse events on women's reproductive health including complications of pregnancy, pelvic inflammatory disease and infertility. The objectives of this project are to define the epidemiology, risk factors, transmission kinetics, and pathogenesis of C. trachomatis infections in different population settings, including populations in resource constrained countries. In a multi-center international trial, we screened a total of 18,014 participants at baseline, 15,054 at 12 months, and 14,243 at 24 months for a variety of STDs using non-invasive molecular amplified assays. The incidence of chlamydia in men was 2.0 per 100 person years both from baseline to 12 months and from 12 to 24 months, and in women, 4.6 from baseline to 12 months and 3.6 from 12 to 24 months; a range of 31.2% to 100% reported no symptoms across the 5 countries. The incidence of gonorrhea in men was 0.3 per 100 person years both from baseline to 12 months and from 12 to 24 months, and in women, 1.4 from baseline to 12 months and 1.1 from 12 to 24 months; a range of 66.7% to 100% reported no symptoms. Being female, aged 18 to 24 years, and having more than 1 partner were associated with both the infections. In addition, being divorced, separated, or widowed was associated with gonorrhea. Being male, having 6+ years of education, and reporting only 1 partner were associated with having no symptoms among those infected with chlamydia. No variables correlated with asymptomatic gonorrhea among those infected. A high prevalence and incidence of asymptomatic sexually transmitted infections was identified among men and women in a wide variety of settings, prompting the need for more effective programs to identify and treat chlamydia and gonorrhea infections. We have used the Internet, www.iwantthekit.org, to offer sampling in Maryland and limited other areas in the U.S. for chlamydia screening in 4,000 women and over 1500 men at home using self-obtained vaginal swabs or self-obtained penile-meatal swabs, which were reported to be highly acceptable. Prevalence for chlamydia for women has been 7.9% overall for women, and 15.3% in young women age 15-19 yr. Both young age and Black race were statistically associated with chlamydia positivity. For men, the overall prevalence has been 7.9%. Initially, over 21% were positive for at least one STD with acceptance for collecting penile swabs being very high. Since 2009, when we offered a rectal self-collection kit, the prevalence for chlamydia in 508 women has been 9.4% and 6.9% in 231 men. We participated in surgical and antibiotic treatment intervention studies in Ethiopia, Niger, and Tanzania in efforts to control trachoma, the most common infectious cause of blindness worldwide. To determine whether infection recurs, we re-examined individuals in Tanzania five years after initiation of the program. Treatment coverage was 80% for all ages in the first year, although coverage 18 months later was lower at 70%. At five years, clinical trachoma rates were still lower than at baseline, ranging from 45% compared to 81% at baseline. After 3 years of mass treatment, the prevalence of trachoma decreased in a linear fashion with number of years of mass treatment, and decreased prevalence of C. trachomatis infection was related to the extent of the previous years azithromycin coverage. Our model suggests that, for communities with baseline trachoma prevalence of 50% and annual treatment coverage of 75%, >7 years of annual mass treatment will be needed to reach a prevalence of trachoma of <5%. In a sub-study of the Tanzania program, all children under 9 years in 4 villages were followed from baseline pre-mass treatment to six months post treatment. 1,991 children under nine years were enrolled in the longitudinal study. Baseline infection was 23.7% and at 6 months was 10.4%, despite 95% coverage. Infection at baseline was positively associated with infection at 6 months (OR = 3.31, 95%CI 2.40-4.56) and treatment had a protective effect (OR = 0.45, 95%CI 0.25-0.80). The age group 2-4 years had an increased risk of infection at 6 months. The household characteristics predictive of infection at 6 months were increasing number of children infected in the household at baseline and increasing number of untreated children in the household. We also studied the ancillary benefits of azithromycin in affecting chlamydia, gonorrhea, malaria, respiratory infections, and diarrhea. The prevalence of genital infections caused by C. trachomatis was 4.2% at baseline before therapy in the mass therapy villages and 2.2% in the control villages. Mass therapy with azithromycin for trachoma in the intervention communities decreased both chlamydia and gonorrhea prevalence below baseline at one month and at 6 months. We plan to continue the mass treatment of villages in Tanzania to determine the frequency of treatment in relationship to control of ocular infections.